In the past year we continued our studies on how intimal thickening develops in polytetrafluoroethylene (PTFE) arterial grafts and in injured arteries in baboons. We have pursued the hypothesis that nitric oxide (NO) is a major negative regulator of smooth muscle cell (SMC) growth in blood vessels, because high blood flow suppresses intimal thickening and induces the endothelial nitric oxide synthase gene (ecNOS). Our experiments with agents to block ecNOS cause vasoconstriction but do not induce SMC proliferation unless there is some degree of injury. In addition, we have performed experiments with antibodies to platelet-derived growth factor receptor-(-( (PDGF-R-(-() to define a role for PDGF in intimal thickening. PDGFR-( blockade inhibits intimal thickening induced by injury or a switch in blood flow. We have also tried to extend our work to clinical application. We have developed an explant system and have shown that SMC growth in explants resembles very closely SMC growth in injured artery. We now hope to use the explant system to define the properties of human SMCs in saphenous vein explants. The ultimate goal is to provide a link between animal studies and outcome in humans.